Pathology of the University Medical Center Schleswig-Holstein, Campus Lübeck and the Research Center Borstel, Leibniz Lung Center, Borstel, Germany.
LungenClinic Großhansdorf, Großhansdorf, Germany.
Clin Epigenetics. 2019 Nov 12;11(1):157. doi: 10.1186/s13148-019-0770-6.
Recently, it was shown that the epigenetic age of non-small cell lung cancer (NSCLC) tissues is different from the chronological age of patients. Here, we demonstrate that Regucalcin and Survivin, molecules which are known to be involved in the process of aging and overcoming aging, are epigenetically modified in NSCLC tissues compared to corresponding tumor-free tissues from the same donors by using methylome bead chip and corresponding transcriptome analyses. A high expression of Survivin on the RNA level was negatively correlated with patients' survival in adenocarcinomas while a high Regucalcin expression was correlated positively. In stage 1 adenocarcinomas, this separation is even sharper for both genes. Within these, adenocarcinomas, smokers with low expression of Survivin show a better outcome, while the high expression of Regucalcin seems to be protective in never smokers. On the protein level, these molecules were detected by immunohistochemistry using tissue microarrays. Since Survivin can be secreted and we observed a high abundance of the protein also in the adjacent immune cells of the tumor microenvironment, an effect on benign cells can be assumed. These findings show that epigenetic re-programming of Survivin and Regucalcin in non-small cell lung cancer leads to enhanced expression of Survivin and reduced expression of Regucalcin, with a possible role of both molecules as predictive markers.
最近，有研究表明非小细胞肺癌（NSCLC）组织的表观遗传年龄与患者的实际年龄不同。在这里，我们通过甲基化珠芯片和相应的转录组分析，证明与同一供体的无肿瘤组织相比，衰老和克服衰老过程中已知涉及的分子Regucalcin 和 Survivin 在 NSCLC 组织中发生了表观遗传修饰。RNA 水平上 Survivin 的高表达与腺癌患者的生存呈负相关，而 Regucalcin 的高表达则呈正相关。在 1 期腺癌中，这两种基因的分离更为明显。在这些腺癌中，低表达 Survivin 的吸烟者预后更好，而 Regucalcin 的高表达在从不吸烟者中似乎具有保护作用。在蛋白质水平上，使用组织微阵列通过免疫组织化学检测到这些分子。由于 Survivin 可以被分泌，并且我们还观察到肿瘤微环境中相邻免疫细胞中存在大量蛋白质，因此可以假设其对良性细胞有影响。这些发现表明非小细胞肺癌中 Survivin 和 Regucalcin 的表观遗传重编程导致 Survivin 表达增强和 Regucalcin 表达降低，这两种分子可能都作为预测标志物发挥作用。
